Statins, 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are often used to lower LDL cholesterol in patients and for protection from atherosclerotic cardiovascular disease, reducing plaque formation in blood vessels and resultant coronary morbidity and mortality in relatively high risk adults. Statins may also be used for pediatric populations with dyslipidemia, the elevation of plasma cholesterol, triglycerides, or both.                It has been found that relatively low doses (40 μM) of simvastatin, lovastatin, and pravastatin each demonstrated reduction in the scar elevation index when compare with a control in a rabbit ear model, which has been described in U.S. patent application Ser. No. 15/407,747, filed Jan. 17, 2017 and now published as US Patent Application Publication Number 2017/0119732. It is desirable to develop compositions that may be applied to and can penetrate the skin and scar tissue. However, the statins exhibit various levels of solubility in water and the previous study reports the use of solvents such as dimethyl sulfoxide (DMSO) or surfactants, which may be relatively toxic and could potentially hinder FDA approval.        
Various efforts have been made to improve solubility of the statins. One method involves the complexation of cyclodextrin (CD) with simvastatin or lovastatin. Another method includes the formation of solid lipid nanoparticles of statin. A further method includes a transdermal niosomes formulation, which contains skin penetrating enhancing surfactants (e.g., Span 20 or Span 60), surface charge imparting agents (e.g., stearylamine or dicetyl phosphate), cholesterol and simvastatin.
Additional liposomal statin formulations have been reported. For example, a liposome simvastatin formulation mainly composed of distearoylphosphatidylcholine (DSPC), distearoyl phosphatidyl glycerol (DSPC, DSPG, Cholesterol:simvastatin at 7:3:1:1 molar ratio) has been reported. Alupei MC formulated liposomal simvastatin and found that it can reduce tumor growth via targeting tumor-associated macrophages-mediated oxidative stress. This liposome statin formulation involves a lipid composition of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (Lipoid GmbH, Ludwigshafen, Germany), polyethylene glycol 2000-distearoylphosphatidylethanolamine (PEG-2000-DSPE), (Lipoid GmbH, Ludwigshafen, Germany), cholesterol (Sigma, St. Louis, USA) and simvastatin (Sigma, St. Louis, USA) in a molar ratio of 17:1.011:1:1.209. This liposomal simvastatin was administrated intravenously (i.v.). Another liposome simvastatin formulation is composed of 1,2-Didodecanoyl-sn-glycero-3-phosphocholine (DLPC) Cholesterol, cholesteryl-polyethylene glycol 600 sebacate (CHOL-PEG), and 1,2-dioleoyl-sn-glycero-3-phosphoric acid monosodium salt (DOPA). Cholesteryl 3β-N-(dimethylaminoethyl) carbamate hydrochloride (CHOL+) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). However, liposome formulations for both relatively soluble and insoluble formations are desired, wherein the formulations provide an increase in solubility of the statins.